Hyponatremia
Conditions
Brief summary
The purpose of this study is to determine if isotonic solutions reduce the risk of hospital acquired hyponatremia compared with hypotonic solutions.
Detailed description
Multicenter, Randomized, Controlled clinical trial. The purpose of this study is to determine if isotonic solutions reduce the risk of hospital acquired hyponatremia compared with hypotonic solutions This study will include 150 patients in 2 groups according to these type of pathology: group 1: medical conditions which includes respiratory problems (pneumonia, bronchiolitis, acute asthma attack) and acute gastrointestinal problems (bacterial or viral gastroenteritis) and group 2: surgical conditions (pre, peri or postoperative patients will be included). Each group will be randomized to receive 3 types of interventions: 0.3% Saline (hypotonic solution), 0.45% Saline (hypotonic solution) or 0.9% Saline (isotonic solution). In non-dehydrated patients the daily total volume of liquid infused will be determined by the volumetric Holliday- Segar\* formula and the daily total volume will be calculated by adding the maintenance requirements (using the Holliday Segar formula) to the fluid deficit (according to percent of estimated weight\*\*) in dehydrated patients. The glucose concentrations in the first group will be 3.3%, and in group 2 and 3 will be 5%. The potassium concentration will be 20mEq/L in all groups. Blood samples will be collected before, 8 hours and 24 hours after the start of intravenous fluid, for the analysis of sodium, potassium, glucose, urea and creatinine. The adverse clinical outcomes at 8 and 24 hours of the start of intravenous fluid will also be recorded. The sodium plasma level, the incidence of hyponatremia and the adverse clinical outcomes will be compared. \*0-10 kilogram (kg): 100ml/kg per day; 10-20 kg: 1000 ml + 50 ml/kg/day over 10 kg; \>20 kg: 1500 ml + 20ml/ kg over 20kg \*\* In patients under 10 kg correspond to a loss of 5% (50 mL/kg) in mild dehydration and 10% in moderate dehydration. In 10 kg or more: 3% (30 mL/kg) in mild dehydration and 6% (60 mL/kg) in moderate dehydration.
Interventions
DRUG0.3% Saline in 3.3% dextrose
Hypotonic Solutions: 0.3% Saline in 3.3% dextrose
Hypotonic Solutions: 0.45% Saline in 5% dextrose
DRUG0.9% Saline in 5% dextrose
Isotonic Solutions 0.9% Saline in 5% dextrose
Sponsors
Tecnologico de Monterrey
Instituto Tecnologico y de Estudios Superiores de Monterey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
3 Months to 15 Years
Healthy volunteers
Yes
Inclusion criteria
* Children between 3 months to 15 years. * Need for intravenous fluids for 8 hours or more. * Normal serum sodium at the beginning of the study of the study (135-145 mEQ/L). * Acute respiratory problems (acute asthma attack, bronchiolitis or pneumonia). * Acute gastrointestinal disorders (viral o bacterial gastroenteritis). * Elective surgical procedures. * Pre, peri o post operative patients (acute appendicitis, intussusception, intestinal perforation, ileus).
Exclusion criteria
* Severe hyponatremia (serum sodium \< 125 mEq/L). * Severe hypernatremia (serum sodium \>155 mEq/L). * Need for intravenous fluids for less than 8 hours according with their treating physician. * Severe dehydration or Shock. * Preexisting chronic diseases (renal diseases, heart diseases or endocrine disorders). * Neurologic diseases. * Head trauma. * Cerebral edema or Intracranial hypertension. * Diabetic ketoacidosis. * Use of diuretics one week or less before the study. * Need for admission to the pediatric critical intensive care unit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital Acquired Hyponatremia | 8 hours | Serum sodium less than 135 mEq/L at 8 hours in a patient with normal serum sodium (135 mEq/L to 145mEq/L) at the beginning of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dysnatraemias at T8 | 8 hours | hyponatraemia (defined as serum sodium \< 135 mmol/L), normonatremia (defined as serum sodium 135-145 mmol/L) or hypernatraemia (defined as serum sodium \> 145 mmol/L) |
| Adverse Reactions Attributed to Acute Plasma Sodium Changes | 8 hours | Adjudicated Morbidity Attributed to Acute Plasma Sodium Changes assessed at 8 hours |
Participant flow
Recruitment details
This trial was conducted in the paediatric and emer- gency departments of the Hospital Regional Materno Infantil de Alta Especialidad in Nuevo Leon, Mexico between August 2013 and February 2014.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: 0.3% Saline in 3.3% Dextrose (Intravenous) Group 1: 0.3% Saline in 3.3% dextrose (intravenous)
0.3% Saline in 3.3% dextrose: Hypotonic Solutions: 0.3% Saline in 3.3% dextrose | 49 |
| Group 2: 0.45% Saline in 5% Dextrose (Intravenous) Group 2: 0.45% Saline in 5% dextrose (intravenous)
0.45% Saline in 5% dextrose: Hypotonic Solutions: 0.45% Saline in 5% dextrose | 50 |
| Group 3: 0.9% Saline in 5% Dextrose (Intravenous) Group 3: 0.9% Saline in 5% dextrose (intravenous)
0.9% Saline in 5% dextrose: Isotonic Solutions 0.9% Saline in 5% dextrose | 52 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Group 3: 0.9% Saline in 5% Dextrose (Intravenous) | Group 1: 0.3% Saline in 3.3% Dextrose (Intravenous) | Group 2: 0.45% Saline in 5% Dextrose (Intravenous) |
|---|---|---|---|---|
| Age, Continuous | 58.9 months STANDARD_DEVIATION 56.5 | 58.8 months STANDARD_DEVIATION 57.7 | 63.5 months STANDARD_DEVIATION 56.1 | 54.6 months STANDARD_DEVIATION 55.9 |
| Dehydration (mild), n | 33 participants | 10 participants | 10 participants | 13 participants |
| Heart rate, bpm | 126 bpm STANDARD_DEVIATION 27 | 128 bpm STANDARD_DEVIATION 28 | 124 bpm STANDARD_DEVIATION 25 | 126 bpm STANDARD_DEVIATION 29 |
| Hypernatremic, n | 2 participants | 2 participants | 0 participants | 0 participants |
| Hyponatraemia, n | 51 participants | 16 participants | 19 participants | 16 participants |
| Normonatremic, n | 98 participants | 34 participants | 30 participants | 34 participants |
| Serum osmolarity, mOsm/L | 279 mOsm/L STANDARD_DEVIATION 8.6 | 281.4 mOsm/L STANDARD_DEVIATION 9.5 | 277.4 mOsm/L STANDARD_DEVIATION 10.6 | 278 mOsm/L STANDARD_DEVIATION 16.2 |
| Serum sodium, mmol/L | 135.5 mmol/L STANDARD_DEVIATION 3 | 135.8 mmol/L STANDARD_DEVIATION 3.2 | 135 mmol/L STANDARD_DEVIATION 2.8 | 135.8 mmol/L STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 66 Participants | 25 Participants | 21 Participants | 20 Participants |
| Sex: Female, Male Male | 85 Participants | 27 Participants | 28 Participants | 30 Participants |
| Systolic blood pressure, mmHg | 100.1 mmHg STANDARD_DEVIATION 10.5 | 99.8 mmHg STANDARD_DEVIATION 11.4 | 101.1 mmHg STANDARD_DEVIATION 11.2 | 99.4 mmHg STANDARD_DEVIATION 9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 49 | 13 / 50 | 11 / 52 |
| serious Total, serious adverse events | 0 / 49 | 0 / 50 | 0 / 52 |
Outcome results
Primary
Hospital Acquired Hyponatremia
Serum sodium less than 135 mEq/L at 8 hours in a patient with normal serum sodium (135 mEq/L to 145mEq/L) at the beginning of the study
Time frame: 8 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: 0.3% Saline in 3.3% Dextrose (Intravenous) | Hospital Acquired Hyponatremia | 10 participants |
| Group 2: 0.45% Saline in 5% Dextrose (Intravenous) | Hospital Acquired Hyponatremia | 11 participants |
| Group 3: 0.9% Saline in 5% Dextrose (Intravenous) | Hospital Acquired Hyponatremia | 1 participants |
Secondary
Adverse Reactions Attributed to Acute Plasma Sodium Changes
Adjudicated Morbidity Attributed to Acute Plasma Sodium Changes assessed at 8 hours
Time frame: 8 hours
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: 0.3% Saline in 3.3% Dextrose (Intravenous) | Adverse Reactions Attributed to Acute Plasma Sodium Changes | 12 Minor Adverse Reactions |
| Group 2: 0.45% Saline in 5% Dextrose (Intravenous) | Adverse Reactions Attributed to Acute Plasma Sodium Changes | 13 Minor Adverse Reactions |
| Group 3: 0.9% Saline in 5% Dextrose (Intravenous) | Adverse Reactions Attributed to Acute Plasma Sodium Changes | 11 Minor Adverse Reactions |
Secondary
Dysnatraemias at T8
hyponatraemia (defined as serum sodium \< 135 mmol/L), normonatremia (defined as serum sodium 135-145 mmol/L) or hypernatraemia (defined as serum sodium \> 145 mmol/L)
Time frame: 8 hours
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1: 0.3% Saline in 3.3% Dextrose (Intravenous) | Dysnatraemias at T8 | Hyponatremia | 23 participants |
| Group 1: 0.3% Saline in 3.3% Dextrose (Intravenous) | Dysnatraemias at T8 | Normonatremia | 26 participants |
| Group 1: 0.3% Saline in 3.3% Dextrose (Intravenous) | Dysnatraemias at T8 | Hypernatremia | 0 participants |
| Group 2: 0.45% Saline in 5% Dextrose (Intravenous) | Dysnatraemias at T8 | Hyponatremia | 20 participants |
| Group 2: 0.45% Saline in 5% Dextrose (Intravenous) | Dysnatraemias at T8 | Normonatremia | 30 participants |
| Group 2: 0.45% Saline in 5% Dextrose (Intravenous) | Dysnatraemias at T8 | Hypernatremia | 0 participants |
| Group 3: 0.9% Saline in 5% Dextrose (Intravenous) | Dysnatraemias at T8 | Normonatremia | 47 participants |
| Group 3: 0.9% Saline in 5% Dextrose (Intravenous) | Dysnatraemias at T8 | Hypernatremia | 2 participants |
| Group 3: 0.9% Saline in 5% Dextrose (Intravenous) | Dysnatraemias at T8 | Hyponatremia | 3 participants |